The bcl-2 gene is overexpressed in non-Hodgkin's lymphoma (NHL), such as small lymphocytic lymphoma (SLL), and many other cancers. Noninvasive imaging of bcl-2 expression has the potential to identify patients at risk for relapse or treatment failure. The purpose of this study was to synthesize and evaluate radiolabeled peptide nucleic acid (PNA)-peptide conjugates targeting bcl-2 gene expression. An 111 In-labeled PNA complementary to the translational start site of bcl-2 messenger RNA was attached to Tyr 3 -octreotate for somatostatin receptor-mediated intracellular delivery. Methods: DOTA-anti-bcl-2-PNA-Tyr 3 -octreotate (1) and 3 control conjugates (DOTA-nonsense-PNATyr 3 -octreotate (2), DOTA-anti-bcl-2-PNA-Ala[3,4,5,6]-substituted congener (3), and DOTA-Tyr 3 -octreotate (4) [DOTA is 1,4,7,10-tetraazacyclododecane-N,N9,N$,N%-tetraacetic acid]) were synthesized by standard solid-phase 9-fluorenylmethoxycarbonyl (Fmoc) chemistry. In vitro studies were performed in Mec-1 SLL cells, which express both bcl-2 messenger RNA and somatostatin receptors. Biodistributions and microSPECT/CT studies were performed in Mec-1-bearing SCID (severe combined immunodeficiency) mice, a new animal model of human SLL. Results: 111 In-Labeled conjugate 1 was taken up by Mec-1 cells through a somatostatin receptor-mediated mechanism. Biodistribution studies showed specific tumor uptake of conjugate 1, the somatostatin analog 4, and the PNA nonsense conjugate 2, but not of the mutant peptide conjugate 3. Mec-1 tumors could be detected by microSPECT/CT using 111 In-labeled DOTA-Tyr 3 -octreotate (4) and the targeted anti-bcl-2 conjugate (1), but not using the 2 negative control conjugates 2 and 3. Conclusion: A new 111 In-labeled antisense PNA-peptide conjugate demonstrated proof of principle for molecular imaging of bcl-2 expression in a new mouse model of human SLL. This imaging agent may be useful for identifying NHL patients at risk for relapse and conventional treatment failure.
Crystalline microporous aluminosilicates (zeolites) efficiently catalyse the transesterification of P-keto esters with high selectivity under environmentally safe reaction conditions.In connection with our ongoing programme on the synthesis of lignans including Podophyllotoxinl 29, we were in need of various intermediate (3-keto esters 23, 24, 27 and 28. (3-Keto esters represent an important class of organic building blocks2 and are used for efficient synthesis of a number of complex natural products. Several methods exist for their synthesis;3 however, none of them are amenable to the present requirement. In this regard, transesterification,4 an important reaction for synthesis of esters, was chosen. Although many methods are available for the preparation of alkyl benzoylacetates,3b~3~,3e there are no reports on the synthesis of p-keto esters 23, 24, 27 and 28. Transesterification of (3-keto esters especially with allylic alcohols is rather difficult as it is offset by facile decarboxylated rearrangement.5 Even modified Taber's method6a gives only moderate yields of allylic acetoacetates.OMe 29
An open-source repository of basic building block models design files for writing chemical formulas, equations, and ionic states are provided. Writing chemical symbols, molecules, and ions in their correct oxidation state or valency in chemical equations is an essential and integral part of learning. For a visually impaired student, it is very difficult to write the molecule arrangements, balance chemical equations, and grasp the knowledge of valence electrons available for bonding and interactions. It is important to provide such students an easy way to understand their formation and manipulation. Emerging technologies like three-dimensional (3D) printing enable us to provide such methods which can help us create working modular molecular and chemical models for tactile perception. The provided scalable models can be readily printed as per the quantity required, to aid sighted learners and blind or low-vision (BLV) learners so that they can learn, understand, and represent elemental and molecular reactions. All the provided models are scalable and identified with Braille labels along with alphanumerical impressions. Further, we have conducted a small survey using the newly created models with BLV learners, and the students responses are also reported here.
Learning to write chemical formulas of compounds is a basic and indispensable part of understanding and studying chemistry. However, it is hard for students with visual impairment to assess and learn molecular arrangements and formulas. For the convenience of such students with special needs, it is necessary to come up with easy, comprehensive, and efficient solutions to make them independent, self-reliant, and be able to control their progress at their own pace. This can be achieved with the aid of emerging new technologies such as 3D printing. In the current research work, a 3D printed model was designed and developed. The open-source repository of 3D printable model design files for the basic building blocks to represent chemical formulas of different elements such as carbon, hydrogen, other elements, and related organic as well as inorganic compounds are being shared freely. These models feature a lock and key design, like jigsaw puzzle pieces, along with Braille and print notation that allow learning to be more interactive, engaging, productive, and effective as the sense of touch (tactile) is one of the primary ways through which visually impaired people perceive physical entities. Each elemental piece in the model is designed specifically as per its available bonding electrons, i.e., valency, allowed only to connect with another complementary element in a unique configuration to ensure their correct arrangement and representation using the lock-and-key feature. The concept of hybridization is also included for enhanced learning.
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